[An approach to the medical management of inflammatory bowel disease (author's transl)].
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Biomedical subjects
Publications and source records attributed to W Bartnik.
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Lamina proprial lymphocytes (LPL), isolated by an EDTA-collagenase technique from patients with various colonic diseases, were investigated for LMIF release in vitro. On stimulation with the preparation of Kunin antigen, macrophage-depleted LPL from patients with severely or moderately active ulcerative colitis showed LMIF release which was significantly greater than that observed using LPL from patients with mild colitis or from those with other diseases of the large bowel, including Crohn's disease. Results similar to those obtained with LPL were found with the corresponding peripheral blood lymphocytes (PBL) stimulated by the preparation of Kunin antigen. In contrast, nonspecific stimulation in vitro with Concanavalin A showed no differences in LMIF releases by the LPL or PBL in the various disease groups. It is suggested that hypersensitivity to Kunin antigen may have pathogenic significance in ulcerative colitis.
For the first time, TG cells have been identified in human colon using EDTA-collagenase-prepared, macrophage-depleted isolates of lamina proprial lymphocytes (LPL). Specimens of human colon were obtained from patients undergoing surgery for idiopathic inflammatory bowel disease (IBD), colorectal cancer (Dukes' B or C), other colonic inflammations or benign polyps. Of additional interest were quantitative findings which showed lower TG values in LPL from patients with IBD, regardless of disease activity or steroid therapy, and in Dukes' Group C cancers, compared to the other groups. However, these differences of TG values were not reflected in the peripheral blood lymphocytes (PBL) in which, compared to healthy controls, the numbers of circulating TG cells were greater in patients with Dukes' B or C cancers and in those with moderately or severely active IBD receiving steroids. These quantitative differences re-emphasize the need for concurrent observations on PBL and LPL in these diseases, particularly in experiments to determine the functional properties of their TG subsets, including mediation of natural killing, antibody-dependent cellular cytotoxicity and their immunoregulatory properties. The identification of TG cells per se in colonic LPL provides a basis for such studies.
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A technique is described, involving sequential treatment of the human colonic mucosa with EDTA in calcium-magnesium-free medium, and with collagenase, to isolate lymphoid cells enriched for intraepithelial (IEL) or lamina proprial lymphocytes (LPL). The IEL and LPL isolates also contained small numbers of eosinophils, mast cells, neutrophils, and macrophages. Plasma cells were present in the LPL but not in the IEL. The IEL isolates contained approximately equal proportions of T, B, and null cells. In contrast, the LPL suspensions contained 52% of T cells, 22% of B cells, and 26% of null cells. The most prevalent membrane immunoglobulin in the two colonic lymphoid cell suspensions was IgA (IEL--53%; LPL--71%). In colonic tissue sections, the percentages of immunoglobulin-containing cells as well as the proportions of cells containing IgA, both in the epithelial layer and the lamina propria, were similar to those found in the suspensions of lymphocytes stained for membrane immunoglobulin. These and other morphologic and characterization data support the contention that the two colonic lymphoid cell populations, obtained by the isolation procedures, were selectively enriched for intraepithelial or lamina proprial lymphocytes, respectively. Thus, this technique provides an important tool for further studies of the functional properties of the gut-associated lymphoid tissues.
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Using an enzymatic method for their isolation, it has been shown that human colonic lamina proprial lymphocytes, isolated from patients with various colonic diseases and depleted of polymorphonuclear leukocytes and macrophages, demonstrated K-cell activity in two antibody-dependent cell-mediated cytotoxicity assays in vitro. No differences were found between the activities of lamina proprial lymphocytes isolated from colonic specimens involved by Crohn's disease, chronic ulcerative colitis, or colonorectal carcinoma. K-cell activity was demonstrable using lymphoid cells isolated from the colons of patients receiving steroid therapy at the time of the therapeutic resections. These findings indicate the need for further investigation of possible roles for K-cells in local immune responses in the human bowel mucosa in inflammatory and neoplastic diseases.
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In 18 patients with ulcerative colitis and in 8 with Crohn's disease two tests were performed simultaneously: a) the leukocyte migration inhibition test using Kunin antigen, and b) titration of serum antibodies against this antigen. Leukocyte migration was studied by the agarose plate technique. At the concentration of 25 microgram/ml, Kunin antigen inhibited migration in five cases of ulcerative colitis and in one with Crohn's disease. This phenomenon was not observed in any of 33 control subjects. All patients in whom leukocyte migration was inhibited were in the active phase of the disease. Titers of antibodies against Kunin antigen were determined by the passive hemagglutination test in an expended group of patients comprising 61 with Crohn's disease. The antibody titer, expressed as the geometric mean of hemagglutinin titers, was nearly three times as high in patients as in 324 healthy controls. The titers were not correlated either with clinical activity of both diseases or with the results of the leukocyte migration inhibition test. The significance of these findings is discussed in the light of other data indicating that Kunin antigen plays a role in the pathogenesis of inflammatory bowel disease.
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